Мутационный профиль генома нормальных и опухолевых клеток у больного множественной миеломой (клиническое наблюдение)
ISSN (print) 1997-6933     ISSN (online) 2500-2139
2023-3
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Ключевые слова

множественная миелома
секвенирование нового поколения
экзом
наследуемые мутации
соматические мутации

Как цитировать

1.
Жук А.С., Кострома И.И., Степченкова Е.И., Качкин Д.В., Белопольская О.Б., Зотова И.В., Гарифуллин А.Д., Волошин С.В., Грицаев С.В., Аксенова А.Ю. Мутационный профиль генома нормальных и опухолевых клеток у больного множественной миеломой (клиническое наблюдение). Клиническая онкогематология. 2024;16(3):337-349. doi:10.21320/2500-2139-2023-16-3-337-349

Ключевые слова

Аннотация

В настоящем исследовании представлено клиническое наблюдение больного с впервые диагностированной множественной миеломой (ММ), у которого до начала лечения проведено секвенирование экзома лимфоцитов периферической крови и опухолевых плазматических клеток CD138+. У пациента выявлено несколько наследуемых вариантов в генах, связанных с предрасположенностью к ММ. В генотипе у пациента обнаружены варианты в генах, отвечающих за репарацию ДНК, в т. ч. наследуемые мутации в генах RFDW3 и TP53. Они участвуют в регуляции стабильности генома, скорости накопления соматических мутаций, в т. ч. структурных перестроек и хромосомных аберраций. На нарушение процессов репарации ДНК у пациента указывает большое количество структурных вариаций и наличие мутационной подписи ID6 в генетическом материале опухоли. Анализ экзома опухолевых клеток позволил определить профиль соматических мутаций, включающий мутации в генах, ранее считавшихся связанными с ММ, а также оценить функциональную значимость выявленных нарушений. Кроме того, среди соматических мутаций мы обнаружили повреждающие мутации и мутации высокой значимости в генах, связанных с развитием других типов опухолей, в частности в генах ASCC3, TETи CHD1, а также в генах, кодирующих антимикробные пептиды CAMP и HTN3. За исключением дополнительной копии плеча 1q в геноме опухолевых плазматических клеток, у пациента не установлено других генетических факторов риска, связанных с неблагоприятным течением заболевания. У больного выявлены наследуемые (мутации в гене ABCB1) и соматические (трисомия по хромосоме 3) изменения генетического материала, которые характеризуются, по данным литературы, как факторы положительного прогноза при ММ.

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